This Program Project is designed to focus investigation of several groups of workers in different departments on experiments which should lead to safer and more consistent results with heart transplantation as a treatment in patients. The projects include immunological studies designed to identify pre-existing immunity to allogeneic cells more sensitively and to ablate such immunity when it is present. Immunological tests of rejection activity are being evaluated and new immunosuppressive regimens with several agents (including cyclosporin A) are being tested. The biology of immune reactions between species (xenografts) is under study. It is apparent that different individuals for one species respond quite differently to the tissues of a single donor of another species. Experiments in which the nature and function of infiltrating cells invading a transplant are underway as are physiological studies of transplanted hearts in animals.